The study aims at identifying protective immune response against severe malaria in young children. This study is based on our earlier studies of pregnancy malaria. Susceptibility to pregnancy malaria (PM) results from the unique binding phenotype of placental parasites that adhere to chondroitin sulfate A (CSA), a molecule that is expressed on the surface of the syncytiotrophoblast and appears throughout the intervillous spaces. Because CSA is not readily accessible for parasite adhesion in the nonpregnant host, women are nave to this parasite subpopulation before their first pregnancy, making first-time mothers most susceptible. Over successive pregnancies women develop specific humoral immunity to placental parasites in the form of anti-adhesion antibodies. Anti-adhesion antibodies are associated with improved pregnancy outcomes. Based on these findings, in the current study we survey the binding phenotype of parasites associated with discrete clinical syndromes collected from children participating in the immune-epi study at Ouelessebougou, Mali, and relate acquisition of anti-adhesion antibodies with protection from severe malaria. The binding phenotype of parasites collected from children is evaluated using a panel of 20 endothelial receptors. Parasites collected from children with severe malaria were more likely to bind to 3 endothelial receptors (P-selectin, Integrin alpha3beta1 and Integrin alpha5beta1) compared to parasites collected from children with uncomplicated malaria. We are currently evaluating the relationship between acquisition of antibodies that block parasite binding to these receptors and protection from severe malaria.